遺傳性出血性血管擴張症之介紹及治療 中山醫學大學附設醫院藥劑科藥師蕭如君 賴永融 李建瑩 中山醫學大學醫學系兼任講師蔡敏鈴 摘要 10~30% - hereditary hemorrhagic telangiectasia osler-weber-rendu syndrome estrogen-progesterone 壹 前言 hereditary hemorrhagic telangiectasia, HHT Osler Weber Rendu Osler-Weber- Rendu syndrome 1 2 貳 遺傳模式 5 HHT HHT1 HHT2 1 HHT1 26 4 Dec. 31 2010 藥學雜誌第 105 冊 69
臨床藥學 Clinical Pharmacy 9 endoglin ENG ENG 2 HHT2 12 ALK-1 activin receptor-like kinase 18q21.1 HHT transforming growth factor beta TGF- 1,3 表一 HHT 相關致病基因 HHT HHT1 ENG endoglin 9q33-34 HHT2 ALK-1 or ACVRL1 Smad4/MADH4 protein product 12q11-q14 18q21.1 HHT3 5q31.3-q32 HHT4 chromosomes 7 參 臨床表徵 1,2 80% 50% 20 30 93% 2,3 16 90% HHT 40 1,4 肆 診斷 HHT curacao criteria 1,2 表二 HHT 之診斷標準 curacao criteria 1. 2. 3. 4. 伍 治療綜論 一 治療原則 HHT 1,3 70 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010
( 一 ) 鼻出血 septodermoplasty 1,2 estrogen-progesterone 5 antifibrinolytic agents 1,3 estrogen progesterone 5-9 ( 二 ) 胃腸道出血 estrogen progesterone antifibrinolytic agents 3,10 H2-blockers proton pump inhibitors 1,4 ( 三 ) 肺部動靜脈畸形 percuteneous transcatheter embolization 1,11 ( 四 ) 腦部動靜脈畸形 1.0 cm neurovascular surgery embolotherapy 1,11 ( 五 ) 肝臟動靜脈畸形 1 二 藥物治療 ( 一 ) 鐵劑 1,3 ( 二 ) 止血劑 ( a n t i f i b r i n o l y t i c agents) tranexamic acid aminocaproic acid HHT 3,10 ( 三 ) 荷爾蒙製劑 (hormonal or anti-hormonal agents) 1. e s t r o g e n progesterone 26 4 Dec. 31 2010 藥學雜誌第 105 冊 71
臨床藥學 Clinical Pharmacy DNA RNA 2,3 6 0.1% estriol ointment 2 / 3 ethinyl estradiol 0.05 mg/day norethisterone 1 mg/day 5-9 1,5 2. tamoxifen 20 mg/day 6 5 ( 四 ) 血管生成抑制劑 (angiogenesis inhibitors) bevacizumab 1 5 表三臨床試驗顯示有療效之荷爾蒙製劑 estrogen estrogen progesteron progesteron androgen anti-estrogen ethinyl estradiol: 0.25-1.0 mg/day 7~10 day methyltesterone dienoestrol 0.01%1 ethinyl estradiol 0.05 mg/day norethisterone1 mg/day norethynodrel 2.5~5 mg/day mestranol 0.075~0.1 mg/day megestrol acetate 180~240 mg/day medroxyprogesterone 10~20 mg/day danazol 200 mg tid tamoxifen 20 mg/day 72 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010
( 五 ) 其它 s i r o l i m u s interferon 1 陸 併發症 1,4 柒 結論 HHT 5 HHT 10% 參考資料 : 1. Claire Shovlin: Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). Retrieved from UpToDate clinical knowledge base, institutional edition. This topic last updated: 2009 8. 2. 2008. 3. Robert A Schwartz: Osler-Weber-Rendu Syndrome. Retrieved from emedicine clinical knowledge base,institutional edition. Last Updated: 2009 May 6. 4. Palda V A, Garcia G, Geisthoff U W et al: International guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia, J Med Genet Published Online First: 2009 June 23. 5. Jameson JJ, Cave DR.: Hormonal and antihormonal therapy for epistaxis in hereditary hemorrhagic telangiectasia, Laryngoscope 2004; 114: 705-9. 6. Hisada T, Kuwabara H, Tsunoda T et al: Hereditary hemorrhagic telangiectasia showing severe anemia which was successfully treated with estrogen, Internal Medicine 1995 ; Vol.34, No.6 pp.589-592. 7. Flessa HC,Glueck HI: Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease). Management of epistaxis in nine patients using systemic hormone therapy, Arch Otolaryngol 1977 Mar; 103(3): 148-51. 8. Vase P: Estrogen treatment of hereditary hemorrhagic telangiectasia. A double-blind controlled clinical trial, Acta Med Scand 1981; 209: 393-6. 9. Hisada T, Kuwabara H, Tsunoda T, et al: Hereditary hemorrhagic telangiectasia showing severe anemia which was successfully treated with estrogen, Intern Med 1995; 34: 589-92. 10. K o r z e n i k J R, To p a z i a n M D, W h i t e R:Treatment of bleeding in hereditary hemorrhagic telangiectasia with aminocaproic acid, N Engl J Med 1994; 331: 1236. 11. Moussouttas M, Fayad P, Rosenblatt M, et al: Pulmonary arteriovenous malformations, cerebral ischemia and neurologic manifestations, Neurology 2000; 55: 959-64. 量器 26 4 Dec. 31 2010 藥學雜誌第 105 冊 73
臨床藥學 Clinical Pharmacy Introduction and Therapy of Hereditary Hemorrhagic Telangiectasia Ju-Chun Shiao 1,Yung-Rung Lai 1, Chien-Ying Lee 1, Min-ling Tsai 2 Department of Pharmacy, Chung-Shan Medical University Hospital 1 School of Medicine, Chung-Shan Medical University 2 Abstract Hereditary hemorrhagic telangiectasia HHT is an autosomal dominant genetic disease of vascular abnormal.ecchymosis is the typical symptom found in mucocutaneous skin lips finger because of hemorrhagic telangiectasia. Recurrent epistaxis occur frequently in childhood. And also occur gastrointestinal bleeding. In addition, arteriovenous malformation can found in the pulmonary liver cerebral. HHT due to the mutation in gene caused their vascular characterized thin walls, narrow tortuous paths.the presence of multiple arteriovenous malformations AVMs that lack intervening capillaries and result in direct connections between arteries and veins.the chronic bleeding cause mild to severe anemia, about 10~30% patients requiring blood transfusion replacement therapy. Hormonal or anti-hormonal therapy and anti-fibrinolytic agents are widely using for treat HHT patients of sever hemmorhagic symptoms. 結晶之美 74 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010